Biochanin A - A G6PD inhibitor: In silico and in vitro studies in non-small cell lung cancer cells (A549).

Secondary metabolites from medicinal plants have a well-established therapeutic potential, with many of these chemicals having specialized medical uses. Isoflavonoids, a type of secondary metabolite, have little cytotoxicity against healthy human cells, making them interesting candidates for cancer treatment. Extensive research has been conducted to investigate the chemo-preventive benefits of flavonoids in treating various cancers. Biochanin A (BA), an isoflavonoid abundant in plants such as red clover, soy, peanuts, and chickpeas, was the subject of our present study. This study aimed to determine how BA affected glucose-6-phosphate dehydrogenase (G6PD) in human lung cancer cells. The study provides meaningful insight and a significant impact of BA on the association between metastasis, inflammation, and G6PD inhibition in A549 cells. Comprehensive in vitro tests revealed that BA has anti-inflammatory effects. Molecular docking experiments shed light on BA's high binding affinity for the G6PD receptor. BA substantially decreased the expression of G6PD and other inflammatory and metastasis-related markers. In conclusion, our findings highlight the potential of BA as a therapeutic agent in cancer treatment, specifically by targeting G6PD and related pathways. BA's varied effects, which range from anti-inflammatory capabilities to metastasis reduction, make it an appealing option for future investigation in the development of new cancer therapeutics.

Comparative transcriptome analysis elucidates positive physiological effects of foliar application of pyraclostrobin on tomato (Solanum lycopersicum L.).

Strobilurins, including pyraclostrobin have frequently been reported showing positive physiological effects in various agricultural crops apart from fungicidal activity. Present study elucidates comparative transcriptome analysis of control and pyraclostrobin treated tomato leaf and identifies metabolic pathways and key genes responsible for positive effects of pyraclostrobin on tomato. Pair-end raw reads, generated by Illumina Hi-seq platform were pre-processed and good quality reads were mapped onto tomato reference genome using HISAT2 alignment programme. Transcript assembly and quantification were performed using StringTie assembler. Differential Gene Expression analysis by DESeq2 identified 1,952 upregulated genes including genes encoding pathogenesis related proteins and 835 downregulated genes. RT-PCR study showed increase in expression of RBCs (2.5-fold), GA20o (3-fold), and NR (1.4-fold) genes, which are the key genes of photosynthesis, gibberellic acid synthesis, and nitrogen assimilation pathways respectively identified in KEGG pathway analysis. Pyraclostrobin treated plants showed 1.6-folds increase in plant height, 3.3-folds increase in number of leaves, and 2.8-folds increase in number of flowers. Total protein content increased 1.7, 1.4, 1.2, 1.2, and 1.4 folds at 1 day after application (DAA), 4DAA, 7DAA, 10DAA, and 13DAA respectively in treated plants. Moreover, content of phenol also increased 1.14, 1.5, 2.4, and 1.5 folds in 4DAA, 7DAA, 10DAA, and 13DAA respectively. Nitrate reductase activity increased 2-fold, 1.8-fold, 1.5-fold and 1.15-fold in 1DAA, 7DAA, 10DAA and 13DAA respectively. Carbohydrate decreased in treated plants up to 7DAA. The present study is the first report of transcriptome analysis elucidating positive physiological effects of strobilurin on plant. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01191-7.

Molecular cloning, heterologous expression, and functional characterization of a cellulolytic enzyme (Cel PRII) from buffalo rumen metagenome.

A cellulase encoding gene, Cel PRII, was identified from Mehsani buffalo rumen metagenome, and cloned and expressed in Escherichia coli BL21(DE3)pLysS. The 1170 bp full length gene encodes a 389 residue polypeptide (Cel PRII) containing a catalytic domain belonging to glycosyl hydrolase (GH) 5 family. The fusion protein consisting of the Cel PRII, thioredoxin tag and 6x Histidine tag with predicted molecular weight of 63 kDa when recovered from inclusion bodies under denaturing conditions, exhibited cellulolytic activity against carboxymethyl cellulose (CMC). Recombinant Cel PRII was stable in the pH range 4.0-10.0 with pH optima 6.0. The optimal reaction temperature of Cel PRII was 30 °C with more than 50% of its activity retained at the temperatures ranging from 0 to 50 °C. Cel PRII exhibited enhanced enzymatic activity in the presence of Mn2+ ions and was inhibited in the presence of chelating agent EDTA. The K m and V max values for CMC were found to be 166 mg/mL and 1292 IU/mg, respectively. Cel PRII identified in the present study may act as an excellent candidate for industrial applications, and may aid in lignocellulosic biomass conversion because of its potential cellulolytic activity, thermostability, and excellent pH stability.

Phytol induces ROS mediated apoptosis by induction of caspase 9 and 3 through activation of TRAIL, FAS and TNF receptors and inhibits tumor progression factor Glucose 6 phosphate dehydrogenase in lung carcinoma cell line (A549).

A number of drugs as well as lead molecules are isolated from natural sources. Phytol is one of such lead molecule belongs to terpenes group distributed widely in medicinal plants. In the present work, we investigated the cytotoxic behavior of phytol on human lung carcinoma cells (A549). Phytol was found to cause characteristic apoptotic morphological changes and generation of ROS in A549 cells. The mechanism of phytol involved the activation of TRAIL, FAS and TNF-α receptors along with caspase 9 and 3. In silico molecular docking studies revealed that phytol has a good binding affinity with glucose-6-phosphate dehydrogenase (G6PD), which is known to promote tumor proliferation. The ability of phytol to become potential drug candidate has been revealed from the pharmacokinetic study performed in the present study.

Maslinic Acid Inhibits Proliferation of Renal Cell Carcinoma Cell Lines and Suppresses Angiogenesis of Endothelial Cells.

Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC) remains a treatment-resistant cancer. As red and processed meat are considered risk factors for RCC, and a vegetable-rich diet is thought to reduce this risk, research into plant-based therapeutics may provide valuable complementary or alternative therapeutics for the management of RCC. Herein, we present the antiproliferative and antiangiogenic effects of maslinic acid, which occurs naturally in edible plants, particularly in olive fruits, and also in a variety of medicinal plants. Human RCC cell lines (ACHN, Caki-1, and SN12K1), endothelial cells (human umbilical vein endothelial cell line [HUVEC]), and primary cultures of kidney proximal tubular epithelial cells (PTEC) were treated with maslinic acid. Maslinic acid was relatively less toxic to PTEC when compared with RCC under similar experimental conditions. In RCC cell lines, maslinic acid induced a significant reduction in proliferation, proliferating cell nuclear antigen, and colony formation. In HUVEC, maslinic acid induced a significant reduction in capillary tube formation in vitro and vascular endothelial growth factor. This study provides a rationale for incorporating a maslinic acid-rich diet either to reduce the risk of developing kidney cancer or as an adjunct to existing antiangiogenic therapy to improve efficacy.